Microchimica Acta ( IF 5.3 ) Pub Date : 2021-08-05 , DOI: 10.1007/s00604-021-04943-6 Alexandre Verdin 1 , Cedric Malherbe 1 , Gauthier Eppe 1
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Highly selective nanoprobes have been developed based on SERS-active Au@Ag nanoparticles protected by a PEG coating and functionalized with monoclonal antibodies against human epidermal growth factor receptor 2 (HER2). The PEG coating allows to drastically reduce unspecific interactions during incubation on tissues, while the monoclonal antibodies allow a highly specific targeting of HER2. Using the designed SERS nanoprobes combined with a spectral imaging and data weighting approach, we demonstrate the proportionality between the SERS signal and the amount of HER2 antigen on the cell membranes as measured by digital image analysis of IHC staining in microscopic breast tumors (linear fit R2 = 0.87). We also show that the level of expression of HER2 measured by SERS is significantly different between several microscopic tumor parts of the same tissue slide. Therefore, SERS is proving to be a suitable technique for the localized quantitative measurement of specific markers in breast cancerous tissues. Owing to its high multiplexing capabilities, SERS could be a future tool of choice for characterizing the molecular heterogeneity of tumors at the microscopic scale.
Graphical abstract
中文翻译：
使用靶向 SERS 成像空间分辨测定显微乳腺肿瘤中 HER2 标记物的丰度
基于由 PEG 涂层保护的 SERS 活性 Au@Ag 纳米粒子开发了高选择性纳米探针，并用针对人表皮生长因子受体 2 (HER2) 的单克隆抗体进行了功能化。PEG 涂层允许在组织孵育期间显着减少非特异性相互作用，而单克隆抗体允许高度特异性地靶向 HER2。使用设计的 SERS 纳米探针结合光谱成像和数据加权方法，我们证明了 SERS 信号与细胞膜上 HER2 抗原量之间的比例，如通过显微乳腺肿瘤中 IHC 染色的数字图像分析（线性拟合R 2= 0.87）。我们还表明，通过 SERS 测量的 HER2 表达水平在同一组织载玻片的几个微观肿瘤部分之间存在显着差异。因此，SERS 被证明是一种适用于乳腺癌组织中特定标志物的局部定量测量的技术。由于其高复用能力，SERS 可能成为未来在微观尺度上表征肿瘤分子异质性的首选工具。
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